0:00:00.840,0:00:02.056 Hi everyone. 0:00:02.080,0:00:04.560 I would like to introduce you to Laika. 0:00:05.680,0:00:09.880 To most of us, Laika is simply[br]a very cute pig. 0:00:10.800,0:00:17.336 However, to hundreds of thousands[br]of patients in need of a lifesaving organ 0:00:17.360,0:00:19.640 Laika is a symbol of hope. 0:00:20.960,0:00:24.056 You see, ever since the 1970s, 0:00:24.080,0:00:27.376 when organ transplants[br]became a real option 0:00:27.400,0:00:31.616 for patients with kidney failure[br]and other organ diseases, 0:00:31.640,0:00:34.240 organ supply has been an issue. 0:00:34.920,0:00:36.816 Over the last few decades, 0:00:36.840,0:00:41.880 the issue only worsened as organ demand[br]has exponentially increased. 0:00:43.400,0:00:45.696 Currently in the US, 0:00:45.720,0:00:49.896 there are close to 115,000 patients 0:00:49.920,0:00:52.680 in need of a lifesaving organ transplant. 0:00:53.520,0:00:55.336 By the end of my talk, 0:00:55.360,0:00:59.120 one more patient[br]will be added to this list. 0:01:00.120,0:01:04.495 Today, about 100 people[br]will get a new organ, 0:01:04.519,0:01:07.336 a chance to start their life anew, 0:01:07.360,0:01:10.336 and yet by the end of today, 0:01:10.360,0:01:12.840 20 others will die waiting. 0:01:14.240,0:01:16.736 The situation is heartbreaking 0:01:16.760,0:01:19.656 for patients, for their families 0:01:19.680,0:01:22.680 and for the doctors who want to do more. 0:01:24.000,0:01:25.936 In some parts of the world, 0:01:25.960,0:01:29.560 the situation also becomes[br]a disturbing social issue. 0:01:30.120,0:01:32.096 In Asia, for example, 0:01:32.120,0:01:36.176 media outlets reported[br]that desperate patients 0:01:36.200,0:01:40.120 are obtaining organs[br]from the cruel black market. 0:01:41.600,0:01:47.016 It is clear that a solution[br]is needed to this crisis. 0:01:47.040,0:01:49.600 Human lives are at stake. 0:01:51.160,0:01:54.216 As a biologist and a geneticist, 0:01:54.240,0:01:57.920 it has become my mission[br]to help solve this problem. 0:01:58.760,0:02:03.776 Today, I am optimistic to say[br]that we are on our way there, 0:02:03.800,0:02:05.000 thanks to Laika. 0:02:05.600,0:02:07.936 Using gene editing technology, 0:02:07.960,0:02:13.816 it's now possible to exquisitely create[br]a human-transplantable organ 0:02:13.840,0:02:16.400 that can be safely grown in pigs. 0:02:17.920,0:02:22.176 Before we jump into the incredible[br]science that makes it happen, 0:02:22.200,0:02:26.600 let's have a better understanding[br]what xenotransplantation is. 0:02:27.120,0:02:31.600 It's a process of transplanting[br]animal organs into humans. 0:02:32.480,0:02:35.496 You may want to ask, why pig organs? 0:02:35.520,0:02:40.336 Because some pigs carry organs[br]with similar size and physiology 0:02:40.360,0:02:41.560 to human organs. 0:02:42.280,0:02:44.696 Over the last half a century, 0:02:44.720,0:02:49.576 pioneers of transplantation[br]have tried hard to make it happen, 0:02:49.600,0:02:52.480 but with limited to no success. 0:02:53.080,0:02:54.280 Why is that? 0:02:54.880,0:02:57.640 Two fundamental hurdles stood in the way. 0:02:58.240,0:03:01.416 First is a problem of rejection. 0:03:01.440,0:03:05.256 When our immune system[br]sees a new organ as foreign, 0:03:05.280,0:03:06.520 it will reject it. 0:03:07.400,0:03:11.720 Second, and this one is specific[br]to the organs from the pig, 0:03:12.760,0:03:17.176 every pig carries a virus[br]that has been native to the pig, 0:03:17.200,0:03:19.856 but can be transmitted into humans. 0:03:19.880,0:03:25.376 It is called the porcine[br]endogenous retrovirus (PERV) 0:03:25.400,0:03:31.400 and this virus has the potential[br]to cause a viral epidemic similar to HIV. 0:03:32.280,0:03:37.056 Without an effective way[br]to address these issues, 0:03:37.080,0:03:42.680 the field of xenotransplantation[br]has been on hold for more than one decade. 0:03:43.600,0:03:47.680 Little progress has been made, until now. 0:03:49.480,0:03:53.160 Let me share with you[br]how I got here today with Laika. 0:03:54.280,0:03:58.296 My journey started[br]from ?? Mountain in China. 0:03:58.320,0:04:02.736 That is the place well described[br]in a lot of legendary stories, 0:04:02.760,0:04:05.400 like the "Crouching Tiger, Hidden Dragon." 0:04:05.840,0:04:08.160 That is the place I call home. 0:04:08.920,0:04:10.656 Growing up in the mountain, 0:04:10.680,0:04:13.760 I started to have[br]a strong connection with nature. 0:04:14.680,0:04:17.736 This is me when I was seven years old 0:04:17.760,0:04:21.176 standing in front[br]of an ancient Buddhist temple 0:04:21.200,0:04:23.216 with a monkey on my shoulder. 0:04:23.240,0:04:26.816 I still vividly remember[br]how my friends and I 0:04:26.840,0:04:30.016 would toss peanuts around[br]to distract the monkeys 0:04:30.040,0:04:32.720 so that we could cross[br]to hike through the valley. 0:04:33.840,0:04:35.336 I loved nature. 0:04:35.360,0:04:38.216 When it was time[br]to choose a field of study, 0:04:38.240,0:04:42.240 I chose to study biology[br]at Peking University in Beijing. 0:04:43.760,0:04:46.256 However, the more I learned, 0:04:46.280,0:04:47.600 the more questions I had. 0:04:48.520,0:04:53.056 How could our genetic makeup[br]be so similar to animals, 0:04:53.080,0:04:55.000 and yet we look so different? 0:04:55.920,0:05:00.776 How is our immune system capable[br]of fighting off so many pathogens 0:05:00.800,0:05:03.520 but smart enough not to attack ourselves. 0:05:04.280,0:05:06.800 Questions like this tormented me. 0:05:07.880,0:05:10.720 I know it sounds nerdy,[br]but you know I'm a scientist. 0:05:12.000,0:05:17.256 After college, I decided[br]I didn't want to just ask the questions, 0:05:17.280,0:05:20.440 I wanted to answer them, so I did. 0:05:21.560,0:05:25.616 In 2008, I was lucky enough to be accepted 0:05:25.640,0:05:29.176 into the PhD program at Harvard University 0:05:29.200,0:05:31.280 and worked with Dr. George Church. 0:05:31.920,0:05:33.656 While working in Church's lab, 0:05:33.680,0:05:38.360 I started to learn and experiment[br]with the genetic makeup of mammals. 0:05:39.200,0:05:41.456 Among all the experiments, 0:05:41.480,0:05:44.680 one particular one[br]took me closer to Laika. 0:05:45.520,0:05:51.456 In 2013, my colleagues and I[br]made changes in a human cell 0:05:51.480,0:05:53.936 using a tool you may have heard about 0:05:53.960,0:05:55.496 called CRISPR. 0:05:55.520,0:05:58.736 We were one of the first two groups 0:05:58.760,0:06:04.136 to report the successful use[br]of such a tool in changing our DNA. 0:06:04.160,0:06:07.680 It was an exciting moment[br]in scientific discovery. 0:06:08.800,0:06:13.136 The gene-editing tool CRISPR[br]has two components. 0:06:13.160,0:06:16.656 It has a scissor called the enzyme CRISPR 0:06:16.680,0:06:19.360 and what is called a guide RNA. 0:06:19.920,0:06:24.056 Think about it as genetic scissors[br]with a microscope. 0:06:24.080,0:06:27.176 The microscope is a guide RNA, 0:06:27.200,0:06:31.216 which brings the scissors[br]to the place we want to cut 0:06:31.240,0:06:33.256 and says, "Here it is," 0:06:33.280,0:06:38.520 and the enzyme CRISPR just cuts[br]and repairs the DNA in the way we want. 0:06:39.720,0:06:42.936 Shortly after we reported our study, 0:06:42.960,0:06:48.896 physicians at Mass General Hospital[br]were intrigued by the medical applications 0:06:48.920,0:06:50.496 of our research. 0:06:50.520,0:06:52.016 They reached out to us, 0:06:52.040,0:06:56.136 and together, we began to see[br]the potential to use CRISPR 0:06:56.160,0:06:58.760 to solve the organ shortage crisis. 0:06:59.840,0:07:01.456 How do we do it? 0:07:01.480,0:07:04.600 It is simple, yet very complex. 0:07:06.080,0:07:12.096 We started by making changes[br]in a pig's cell to make it virus-free 0:07:12.120,0:07:14.896 and human-immune-compatible. 0:07:14.920,0:07:19.696 The nucleus of that cell[br]is then implanted into a pig egg 0:07:19.720,0:07:22.616 and allowed to divide into an embryo. 0:07:22.640,0:07:27.936 The resulting embryo is then placed[br]into the uterus of a surrogate mother 0:07:27.960,0:07:30.000 and allowed to divide into a pig. 0:07:30.680,0:07:33.040 Basically, it's a process of cloning. 0:07:33.760,0:07:37.616 The piglet then carries organs[br]whose genetic makeup 0:07:37.640,0:07:41.240 hopefully wouldn't be rejected[br]by the human immune system. 0:07:42.960,0:07:49.376 In 2015, our team decided to tackle[br]the viral transmission problem first. 0:07:49.400,0:07:55.576 We wanted to take out[br]all 62 copies of the PERV virus 0:07:55.600,0:07:57.000 from the pig genome, 0:07:58.200,0:08:02.336 but at the time,[br]it was nearly mission impossible. 0:08:02.360,0:08:03.776 Even with CRISPR, 0:08:03.800,0:08:08.616 we could only do one or two[br]modifications within a cell. 0:08:08.640,0:08:15.176 The record for number of modifications[br]we can do in a particular cell was five. 0:08:15.200,0:08:20.440 We had to increase the throughput[br]by more than tenfold to achieve that. 0:08:21.400,0:08:25.056 With very careful design[br]and hundreds of trials, 0:08:25.080,0:08:28.296 we successfully took out all the virus, 0:08:28.320,0:08:29.896 broke the record. 0:08:29.920,0:08:32.376 More importantly, our studies showed 0:08:32.400,0:08:37.456 that we could eliminate[br]the possibility of this dangerous virus 0:08:37.480,0:08:39.799 being transmitted into humans. 0:08:41.080,0:08:45.456 Last year, with a modified cell[br]and cloning technology, 0:08:45.480,0:08:49.320 our startup, eGenesis, produced Laika, 0:08:50.160,0:08:54.640 the first pig of its kind[br]born without PERV. 0:08:55.480,0:08:59.216 (Applause) 0:08:59.240,0:09:03.216 Laika represents the first critical step 0:09:03.240,0:09:06.976 in establishing safe xenotransplantation. 0:09:07.000,0:09:08.896 It is also a platform 0:09:08.920,0:09:11.896 that we can do further[br]genetic modification on 0:09:11.920,0:09:14.120 to solve the immunology problem. 0:09:14.760,0:09:19.856 Since then, we have created[br]more than 30 pigs without PERV, 0:09:19.880,0:09:25.480 and they may be the most advanced[br]geno-modified animal living on Earth. 0:09:26.400,0:09:29.696 We named Laika after the Soviet dog 0:09:29.720,0:09:33.040 who was the first animal[br]to orbit the Earth. 0:09:33.600,0:09:36.576 We hope Laika and her siblings 0:09:36.600,0:09:41.400 can lead us into a new frontier[br]of science and medicine. 0:09:43.360,0:09:48.496 Imagine a world where patients[br]who suffer from liver failure 0:09:48.520,0:09:51.176 can be saved with a new liver 0:09:51.200,0:09:54.256 without having to wait for a donation 0:09:54.280,0:09:56.080 or another human to die. 0:09:57.600,0:10:01.696 Imagine a world where people with diabetes 0:10:01.720,0:10:05.456 do not have to rely[br]on insulin after every meal 0:10:05.480,0:10:09.576 because we can provide them[br]with good pancreatic cells 0:10:09.600,0:10:11.880 that can produce insulin on their own. 0:10:12.600,0:10:17.576 And imagine a world[br]where patients with kidney failure 0:10:17.600,0:10:21.280 do not have to face[br]the burden of dialysis. 0:10:22.320,0:10:26.056 We are striving to create that world, 0:10:26.080,0:10:28.880 a world without organ shortage. 0:10:29.720,0:10:33.456 We finally have the tool[br]to tackle the problem 0:10:33.480,0:10:35.616 we could never tackle before, 0:10:35.640,0:10:38.920 and Laika is just[br]the beginning of our journey. 0:10:40.040,0:10:43.576 We have to be very humble[br]in front of nature, 0:10:43.600,0:10:46.216 because there are more issues[br]to be addressed, 0:10:46.240,0:10:47.856 including immunology 0:10:47.880,0:10:51.840 and things we couldn't even[br]anticipate at this point. 0:10:52.760,0:10:58.896 However, it is our responsibility[br]to translate the cutting-edge science 0:10:58.920,0:11:04.240 into medicine to save the lives[br]of all the patients who are waiting. 0:11:05.480,0:11:06.736 Thank you very much. 0:11:06.760,0:11:11.600 (Applause) 0:11:17.800,0:11:21.296 Chris Anderson: I mean, Luhan,[br]this is extraordinary work here. 0:11:21.320,0:11:22.520 Come forward. 0:11:23.640,0:11:28.056 So what's the next steps here?[br]You've got rid of the virus. 0:11:28.080,0:11:30.416 The next steps involve[br]trying to get to the point 0:11:30.440,0:11:34.216 where a human body[br]won't reject a transplant. 0:11:34.240,0:11:36.040 What's involved in solving that? 0:11:37.160,0:11:39.416 Luhan Yang: It's a very[br]complicated process. 0:11:39.440,0:11:43.896 So we need to take out[br]the antigen of the pigs. 0:11:43.920,0:11:47.336 In addition, we can learn[br]a lot from cancer. 0:11:47.360,0:11:51.536 How can cancer invade[br]or circumvent our immune system 0:11:51.560,0:11:56.016 so that we can utilize the trick of cancer 0:11:56.040,0:11:58.376 and implement that on the pig organ 0:11:58.400,0:12:01.480 to fool our immune system[br]to not attack the organ. 0:12:03.680,0:12:07.056 CA: When would you estimate,[br]when do you hope 0:12:07.080,0:12:10.400 that the first successful[br]transplant would happen? 0:12:11.360,0:12:15.240 LY: It would be irresponsible for me[br]to give you any number. 0:12:16.200,0:12:18.320 CA: We're at TED.[br]We're always irresponsible. 0:12:18.760,0:12:20.496 LY: But we are working day and night 0:12:20.520,0:12:22.600 trying to make this happen[br]for the patients. 0:12:23.440,0:12:26.336 CA: So not even, you won't say[br]that you think it could happen 0:12:26.360,0:12:28.736 within a decade or within[br]five years or something? 0:12:28.760,0:12:31.160 LY: For sure we hope it happens[br]within one decade. 0:12:32.080,0:12:34.016 (Laughter) 0:12:34.040,0:12:37.656 CA: So there's a lot of people here[br]who would be very, very excited at that, 0:12:37.680,0:12:39.176 the potential is extraordinary. 0:12:39.200,0:12:41.616 There will be some other[br]people here who are going, 0:12:41.640,0:12:42.896 "That pig is too cute. 0:12:42.920,0:12:47.496 Humans shouldn't be exploiting[br]something so cute for our benefit." 0:12:47.520,0:12:49.960 Do you have any response to that? 0:12:51.120,0:12:52.376 LY: Yeah, sure. 0:12:52.400,0:12:57.296 So imagine one pig[br]can save eight people's lives. 0:12:57.320,0:13:00.416 In addition, similar to human donation, 0:13:00.440,0:13:03.176 if we only harvest[br]one kidney from the pig, 0:13:03.200,0:13:05.096 the pig can still be alive, 0:13:05.120,0:13:09.176 so we are very mindful about the issues, 0:13:09.200,0:13:13.576 but I think our goal is just to address[br]the unmet medical need 0:13:13.600,0:13:16.296 for those patients and their families. 0:13:16.320,0:13:19.600 CA: Plus, no one can say that to you[br]if they eat bacon, right? 0:13:20.440,0:13:21.656 LY: That's a good point. 0:13:21.680,0:13:23.136 (Laughter) 0:13:23.160,0:13:25.616 CA: Luhan, thank you so much.[br]LY: Thank you so much. 0:13:25.640,0:13:27.880 (Applause)